Brain TumorPhase 1/2NCT05588141
000860: A Phase I/II Study of Zotiraciclib for Recurrent Malignant Gliomas With Isocitrate Dehydrogenase 1 or 2 (IDH1 or IDH2) Mutations
A Phase 1/2 study testing Zotiraciclib in people with Brain Tumor and Cancer, run by National Cancer Institute (NCI) at 2 sites in United States.
Trial summary
Protocol # 000860 Background: Diffuse gliomas are tumors that affect the brain and spinal cord. Gliomas that develop in people with certain gene mutations (IDH1 or IDH2) are especially aggressive. Better treatments are needed. Read more about this study
- Who is it for?
- Ages 15 to 99 years
- Conditions the study is for
- Brain Tumor, Cancer
- What is being tested?
- Zotiraciclib
- Type of treatment
- Pill or oral medicine
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 96 participants
- Where
- 2 sitesUnited States
- Study dates
- 16 May 2023to 2 Aug 2032
- Phase
- Phase 1/2
- Are there results?
- Not yet: the study is under way
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 15 to 99 years
- All sexes
- No healthy volunteers
- Child, Adult, Older adult
Who may be able to join
- Participants must have diffuse glioma, WHO grades 2-4, histologically confirmed by certified neuropathologistI.
- IDH1 or IDH2 mutation status confirmed by TruSight(TM) Oncology 500 performed in LP, NCI or prior documentation of IDH1 or IDH2 mutation status
- Participants must have received prior treatment (e.g., radiation, conventional chemotherapy, or vorasidenib) prior to disease progression.
- Participants must have recurrent disease, proven histologically or by imaging studies
- Participants who have undergone prior surgical resection are eligible for enrollment to cohorts 1-4.
- Age >15 years
Show all 21Show fewer
- Karnofsky >70%
- Participants must have adequate organ and marrow function as defined below:
- leukocytes >=3,000/microliter
- absolute neutrophil count (ANC) >=1,500/microliter
- platelets >100,000/microliter
- total bilirubin <=2x ULN (ULN 1.3 mg/dl) except for participants with Gilbert Syndrome
- AST < 3x ULN (ULN 34U/L)
- ALT < 3x ULN (ULN 55U/L)
- serum creatinine < 1.5 mg/dL
- calculated creatinine clearance by CKD-EPI equation > 60 cc/min
- Participants must have recovered from the adverse effects of prior therapy to grade 2 or less (per Common Terminology Criteria for Adverse Events (CTCAE) version 5.0)
- Individuals of child-bearing potential (IOCBP) and men must agree to use highly effective contraception (hormonal, intrauterine device (IUD), abstinence, tube ligation, partner has had a previous vasectomy) at the study entry, for the duration of study treatment, and up to 3 months after the last dose of zotiraciclib
- Breastfeeding participants must be willing to discontinue breastfeeding from study treatment initiation through 3 months after study treatment discontinuation
- Participants must be scheduled for brain tumor biopsy or surgical resection at NIH (Cohort 5 only)
- The ability of a participant, parent or legal guardian of minor participant to understand and the willingness to sign a written informed consent document. No Legally Authorized Representative can provide initial consent.
Who cannot join
- More than one disease relapse in those with initial diagnosis of WHO grade 3-4, or more than two disease relapses in those with initial diagnosis of WHO grade 2 for Phase II. For Phase I enrollment, there are no limits on the number of prior recurrences.
- Prior therapy with:
- any investigational agent (including IDH mutant inhibitor) and/or standard of care cytotoxic therapy within 28 days prior to treatment initiation
- vincristine within 14 days prior to treatment initiation
- nitrosoureas within 42 days prior to treatment initiation
- procarbazine within 21 days prior to treatment initiation
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- non-cytotoxic agents, e.g., interferon, tamoxifen, thalidomide, cis-retinoic acid, within 7 days prior to treatment initiation
- surgery within 14 days prior to treatment initiation
- radiation therapy within 30 days prior to treatment initiation
- bevacizumab for tumor treatment. Note: participants who received bevacizumab for symptom management, including but not limited to cerebral edema, or pseudo progression can be enrolled
- Prolonged QTc >470ms as calculated by correction formula on screening electrocardiogram (ECG) (QTCf can be used; QTCb can be used for participants with sinus bradycardia)
- Prior invasive malignancies within the past 3 years prior to study treatment initiation (with the exception of non-melanoma skin cancers, carcinoma in situ of the cervix, melanoma in situ, or any localized cancer for whom the systemic standard of care therapy is not required)
- History of allergic reactions attributed to compounds of similar chemical composition to zotiraciclib, such as flavopiridol
- Pregnancy (confirmed with beta-HCG serum or urine pregnancy test performed at screening)
- Uncontrolled intercurrent illness or social situations that would limit compliance with study requirements
- Uncontrolled primary diabetes mellitus
Trial locations and contacts
2 sites in 1 country. Contact the study team or a site near you to ask about taking part.
United States2 sites, 2 recruiting
- Recruiting
National Institutes of Health Clinical Center
Bethesda, Maryland, 20892
National Cancer Institute Referral Office, 888-624-1937
- Recruiting
Mayo Clinic Flordia
Jacksonville, Florida, 32224
Christine Cordova, M.D., 240-760-7691, christine.cordova@nih.gov
About this study
Official title: A Phase I/II Study of Zotiraciclib for Recurrent Malignant Gliomas With Isocitrate Dehydrogenase 1 or 2 (IDH1 or IDH2) Mutations
Protocol # 000860
Background:
Read more
Diffuse gliomas are tumors that affect the brain and spinal cord. Gliomas that develop in people with certain gene mutations (IDH1 or IDH2) are especially aggressive. Better treatments are needed.
Objective:
To see if a study drug (zotiraciclib) is effective in people with recurrent diffuse gliomas who have IDH1 or IDH2 mutations.
Eligibility:
People aged 15 years and older with diffuse gliomas that returned after treatment. They must also have mutations in the IDH1 or IDH2 genes.
Design:
Participants will be screened. They will have a physical exam with blood and urine tests. They will have tests of their heart function. They will have an MRI of their brain. A new biopsy may be needed if previous results are not available.
Zotiraciclib is a capsule taken by mouth with a glass of water. Participants will take the drug at home on days 1, 4, 8, 11, 15, and 18 of a 28-day cycle. They may also be given medications to prevent side effects of the study drug. The schedule for taking the study drug may vary for participants who will undergo surgery.
Participants will be given a medication diary for each cycle. They will write down the date and time of each dose of the study drug.
Participants will visit the clinic about once a month. They will have a physical exam, blood tests, and tests to evaluate their heart function. An MRI of the brain will be repeated every 8 weeks.
Participants may remain in the study for up to 18 cycles (1.5 years).
Read the detailed description
Background:
- Zotiraciclib is a multi-kinase inhibitor that has been shown to have anti-glioma effects through transcriptional suppression, mitochondrial dysfunction, and adenosine 5'-triphosphate (ATP) reduction in glioblastoma in our preclinical studies
- Zotiraciclib is orally administered and likely penetrates the blood brain barrier (BBB). There has been a clinical experience in using zotiraciclib as a single agent and in combination with other chemotherapy agents in cancers, including malignant gliomas
- Our phase I study of zotiraciclib and temozolomide (TMZ) in recurrent high-grade astrocytomas determined the maximum tolerated dose (MTD) of zotiraciclib in combination with TMZ and demonstrated the safety of the treatment in recurrent high-grade glioma patients
- Preliminary efficacy analysis of Phase I demonstrated an improved response to zotiraciclib in combination with TMZ in IDH-mutant gliomas compared to the IDH-wildtype counterpart
- A selective vulnerability to zotiraciclib as a single agent was demonstrated in the preclinical models of IDH-mutant gliomas
Objectives:
- Phase I: To estimate recommended phase II dose (RP2D) of zotiraciclib
- Phase II: To determine 12-months progression free survival (PFS) in participants with recurrent glioma, IDH1/2-mutant, World Health Organization (WHO) grade 3 treated with zotiraciclib in comparison with the established brain tumor database matched for tumor molecular characteristics and clinical prognostic factors
Eligibility:
- Age >=15; Karnofsky performance status (KPS) >=70%
- Histological confirmation of diffuse glioma, WHO grades 2-4 with IDH1/2 mutation status confirmed by DNA sequencing
- Have recurrent disease
- Have prior treatment of radiation and/or conventional chemotherapies
- No prior use of bevacizumab as a treatment for a brain tumor
Design:
- This is a phase I/II study to evaluate the safety and efficacy of zotiraciclib as a single agent in recurrent IDH-mutant gliomas.
- Initially, 9-24 participants (Cohort 1) will be assigned to Phase I to estimate recommended phase 2 dose (RP2D) of zotiraciclib.
- Once RP2D is estimated, we will start enrollment into cohorts for Phase II, non-surgical participants (Cohorts 2-4), and surgical (Cohort 5). This trial plans to enroll up 64 evaluable participants.
- Drug will be administered on days 1, 4, 8, 11, 15, 18 in cycles of 28 days for a maximum of 18 cycles. Starting dose is 200 mg. In the case that 200 mg is not tolerable, a lower dose 150 mg, will be evaluated. If 200 mg is tolerated well, a higher dose level will be evaluated at 250 mg.
- Participants in the surgical cohort will get an additional single pre-treatment with one dose of study drug at the RP2D on Day 1 of Cycle 0, followed by brain tumor biopsy or surgical resection within 24 hours on Day 2 of Cycle 0. Approximately 2-4 weeks after surgery or biopsy participants in this Cohort will continue treatment with the study drug and start Day 1 of Cycle 1.
- Conditions
- Brain Tumor, Cancer
- Being tested
- Zotiraciclib
- Keywords
- Brain Tumor, Glioma, Idh Mutation, Recurrent Disease
- Medical subject headings
- Brain Neoplasms, Neoplasms, Glioma, Recurrence
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
ZotiraciclibDrug
Zotiraciclib will be given orally at the DL1, DL-1, or DL 2 once a day on days 1, 4, 8, 11, 15, 18 of every 28-days cycle (18 cycles total).
| Study group | Role | What they receive |
|---|---|---|
| 1 (Closed to Enrollment) | Experimental | Escalation/de-escalation dose levels of zotiraciclib given in 28 day cycles Receives: Drug: Zotiraciclib |
| 2 | Experimental | Estimated RP2D of zotiraciclib given in 28 day cycles Receives: Drug: Zotiraciclib |
| 3 | Experimental | One RP2D dose of zotiraciclib given on the day prior to brain tumor biopsy or resection, a continuation of treatment with estimated RP2D of zotiraciclib given in 28 days cycles following the recovery of the surgery Receives: Drug: Zotiraciclib |
What is being measured
The primary outcome is the main question the study is designed to answer.
To determine 12 months PFS in participants w/ recurrent glioma, IDH1/2-mutant, WHO grade 3 treated w/ zotiraciclib in comparison w/ the established brain tumor database matched for tumor molecular characteristics and clinical prognostic factors
Proportion of patients that have progressive disease after 12 months
Measured: 12 Months
To estimate recommended phase II dose (RP2D) of zotiraciclib
Number of DLTs within the DLT Period
Measured: 28 days
Secondary outcomes (3)
To determine the efficacy of treatment with zotiraciclib in participants with recurrent glioma, IDH1/2-mutant WHO grade 3 in comparison with the established brain tumor database by 3 years PFS rate
Amount of time until disease progression from initiation of study therapy as compared with data of the brain tumor database
Measured: 3 years
To determine the safety of zotiraciclib in participants with recurrent glioma, IDH1/2-mutant WHO grades 2-4
Type, grade and frequency of adverse events
Measured: Day 1 of Cycle 0 (Cohort 5) or Day 1 of Cycle 1 (Cohorts 1-4) through 30 days after the study agent was last administered will be collected on the days study drug is administered, and at the safety follow up visit.
To determine the efficacy of treatment with zotiraciclib in participants with recurrent glioma, IDH1/2-mutant WHO grade 3 in comparison with the established brain tumor database by 5 years overall survival (OS) rate
Amount of time subject survives after initiation of study therapy as compared with data of the brain tumor database
Measured: 5 years
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted20 Oct 2022
- Study start16 May 2023
- Primary completion1 Aug 2028 (estimated)
- Study completion2 Aug 2032 (estimated)
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Publications (5)Papers the sponsor has linked to this study.
- Other trials for Brain TumorStudies of the same condition, open and under way.
- More trials run by National Cancer Institute (NCI)The sponsor's other registered studies.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 1/2
- Primary purpose
- Treatment
- Allocation
- Non-randomised
- Intervention model
- Parallel groups
- Masking
- None (open label)
- Enrolment
- 96 participants (estimated)
Sponsor and investigators
- Lead sponsor
- National Cancer Institute (NCI)
- Sponsor type
- US National Institutes of Health
- Responsible party
- Sponsor
- Investigators
- Kevin A Camphausen, M.D., Principal investigator, National Cancer Institute (NCI)
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT05588141
- Sponsor's protocol ID
- 10000860
- Other IDs
- 000860-C
- Status last verified
- 15 Oct 2026
- First submitted
- 15 Oct 2022
- Last updated
- 29 Oct 2026
- Results posted
- No
- FDA-regulated drug
- Yes
- FDA-regulated device
- No
- Individual data sharing
- Yes: All IPD recorded in the medical record will be shared with intramural investigators upon request. In addition, all large scale genomic sequencing data will be shared with subscribers to dbGaP.
Publications
Yuan Y, Hess KR, Hilsenbeck SG, Gilbert MR. Bayesian Optimal Interval Design: A Simple and Well-Performing Design for Phase I Oncology Trials. Clin Cancer Res. 2016 Sep 1;22(17):4291-301. doi: 10.1158/1078-0432.CCR-16-0592. Epub 2016 Jul 12.
PubMed 27407096Miller JJ, Loebel F, Juratli TA, Tummala SS, Williams EA, Batchelor TT, Arrillaga-Romany I, Cahill DP. Accelerated progression of IDH mutant glioma after first recurrence. Neuro Oncol. 2019 May 6;21(5):669-677. doi: 10.1093/neuonc/noz016.
PubMed 30668823Wu J, Yuan Y, Long Priel DA, Fink D, Peer CJ, Sissung TM, Su YT, Pang Y, Yu G, Butler MK, Mendoza TR, Vera E, Ahmad S, Bryla C, Lindsley M, Grajkowska E, Mentges K, Boris L, Antony R, Garren N, Siegel C, Lollo N, Cordova C, Aboud O, Theeler BJ, Burton EM, Penas-Prado M, Leeper H, Gonzales J, Armstrong TS, Calvo KR, Figg WD, Kuhns DB, Gallin JI, Gilbert MR. Phase I Study of Zotiraciclib in Combination with Temozolomide for Patients with Recurrent High-grade Astrocytomas. Clin Cancer Res. 2021 Jun 15;27(12):3298-3306. doi: 10.1158/1078-0432.CCR-20-4730. Epub 2021 Mar 30.
PubMed 33785481Pang Y, Li Q, Sergi Z, Yu G, Kim O, Lu P, Chan M, Sang X, Wang H, Ranjan A, Robey RW, Soheilian F, Tran B, Nunez FJ, Zhang M, Song H, Zhang W, Davis D, Gilbert MR, Gottesman MM, Liu Z, Thomas CJ, Castro MG, Gujral TS, Wu J. Exploiting the therapeutic vulnerability of IDH-mutant gliomas with zotiraciclib. iScience. 2025 Mar 25;28(4):112283. doi: 10.1016/j.isci.2025.112283. eCollection 2025 Apr 18.
PubMed 40241769Pang Y, Li Q, Sergi Z, Yu G, Sang X, Kim O, Wang H, Ranjan A, Merchant M, Oudit B, Robey RW, Soheilian F, Tran B, Nunez FJ, Zhang M, Song H, Zhang W, Davis D, Gilbert MR, Gottesman MM, Liu Z, Khan J, Thomas CJ, Castro MG, Gujral TS, Wu J. Exploiting the therapeutic vulnerability of IDH-mutant gliomas with zotiraciclib. bioRxiv [Preprint]. 2024 Jan 2:2023.06.29.547143. doi: 10.1101/2023.06.29.547143.
PubMed 37786680
Study at a glance
From the registry record, last updated by the sponsor on 29 Oct 2026. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- A Phase I/II Study of Zotiraciclib for Recurrent Malignant Gliomas With Isocitrate Dehydrogenase 1 or 2 (IDH1 or IDH2) Mutations
- ClinicalTrials.gov ID
- NCT05588141
- Acronym / sponsor ID
- 10000860
- Conditions
- Brain Tumor, Cancer
- Keywords
- Brain Tumor, Glioma, Idh Mutation, Recurrent Disease
- Phase
- Phase 1/2
- Study type
- Interventional
- Recruitment status
- Recruiting
- Enrolment
- 96 participants (estimated)
- Lead sponsor
- National Cancer Institute (NCI)US National Institutes of Health
- Study start
- 16 May 2023 (actual)
- Primary completion
- 1 Aug 2028 (estimated)
- Study completion
- 2 Aug 2032 (estimated)
- First posted
- 20 Oct 2022 (actual)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
Protocol # 000860
Background:
Diffuse gliomas are tumors that affect the brain and spinal cord. Gliomas that develop in people with certain gene mutations (IDH1 or IDH2) are especially aggressive. Better treatments are needed.
Objective:
To see if a study drug (zotiraciclib) is effective in people with recurrent diffuse gliomas who have IDH1 or IDH2 mutations.
Eligibility:
People aged 15 years and older with diffuse gliomas that returned after treatment. They must also have mutations in the IDH1 or IDH2 genes.
Design:
Participants will be screened. They will have a physical exam with blood and urine tests. They will have tests of their heart function. They will have an MRI of their brain. A new biopsy may be needed if previous results are not available.
Zotiraciclib is a capsule taken by mouth with a glass of water. Participants will take the drug at home on days 1, 4, 8, 11, 15, and 18 of a 28-day cycle. They may also be given medications to prevent side effects of the study drug. The schedule for taking the study drug may vary for participants who will undergo surgery.
Participants will be given a medication diary for each cycle. They will write down the date and time of each dose of the study drug.
Participants will visit the clinic about once a month. They will have a physical exam, blood tests, and tests to evaluate their heart function. An MRI of the brain will be repeated every 8 weeks.
Participants may remain in the study for up to 18 cycles (1.5 years).
Detailed description
Background:
- Zotiraciclib is a multi-kinase inhibitor that has been shown to have anti-glioma effects through transcriptional suppression, mitochondrial dysfunction, and adenosine 5'-triphosphate (ATP) reduction in glioblastoma in our preclinical studies
- Zotiraciclib is orally administered and likely penetrates the blood brain barrier (BBB). There has been a clinical experience in using zotiraciclib as a single agent and in combination with other chemotherapy agents in cancers, including malignant gliomas
- Our phase I study of zotiraciclib and temozolomide (TMZ) in recurrent high-grade astrocytomas determined the maximum tolerated dose (MTD) of zotiraciclib in combination with TMZ and demonstrated the safety of the treatment in recurrent high-grade glioma patients
- Preliminary efficacy analysis of Phase I demonstrated an improved response to zotiraciclib in combination with TMZ in IDH-mutant gliomas compared to the IDH-wildtype counterpart
- A selective vulnerability to zotiraciclib as a single agent was demonstrated in the preclinical models of IDH-mutant gliomas
Objectives:
- Phase I: To estimate recommended phase II dose (RP2D) of zotiraciclib
- Phase II: To determine 12-months progression free survival (PFS) in participants with recurrent glioma, IDH1/2-mutant, World Health Organization (WHO) grade 3 treated with zotiraciclib in comparison with the established brain tumor database matched for tumor molecular characteristics and clinical prognostic factors
Eligibility:
- Age >=15; Karnofsky performance status (KPS) >=70%
- Histological confirmation of diffuse glioma, WHO grades 2-4 with IDH1/2 mutation status confirmed by DNA sequencing
- Have recurrent disease
- Have prior treatment of radiation and/or conventional chemotherapies
- No prior use of bevacizumab as a treatment for a brain tumor
Design:
- This is a phase I/II study to evaluate the safety and efficacy of zotiraciclib as a single agent in recurrent IDH-mutant gliomas.
- Initially, 9-24 participants (Cohort 1) will be assigned to Phase I to estimate recommended phase 2 dose (RP2D) of zotiraciclib.
- Once RP2D is estimated, we will start enrollment into cohorts for Phase II, non-surgical participants (Cohorts 2-4), and surgical (Cohort 5). This trial plans to enroll up 64 evaluable participants.
- Drug will be administered on days 1, 4, 8, 11, 15, 18 in cycles of 28 days for a maximum of 18 cycles. Starting dose is 200 mg. In the case that 200 mg is not tolerable, a lower dose 150 mg, will be evaluated. If 200 mg is tolerated well, a higher dose level will be evaluated at 250 mg.
- Participants in the surgical cohort will get an additional single pre-treatment with one dose of study drug at the RP2D on Day 1 of Cycle 0, followed by brain tumor biopsy or surgical resection within 24 hours on Day 2 of Cycle 0. Approximately 2-4 weeks after surgery or biopsy participants in this Cohort will continue treatment with the study drug and start Day 1 of Cycle 1.
Study design
- Primary purpose
- Treatment
- Allocation
- Non-randomised
- Intervention model
- Parallel groups
- Masking
- None (open label)
- Number of arms
- 3
| Arm | Type | Receives |
|---|---|---|
| 1 (Closed to Enrollment) | Experimental | Drug: ZotiraciclibEscalation/de-escalation dose levels of zotiraciclib given in 28 day cycles |
| 2 | Experimental | Drug: ZotiraciclibEstimated RP2D of zotiraciclib given in 28 day cycles |
| 3 | Experimental | Drug: ZotiraciclibOne RP2D dose of zotiraciclib given on the day prior to brain tumor biopsy or resection, a continuation of treatment with estimated RP2D of zotiraciclib given in 28 days cycles following the recovery of the surgery |
Who may qualify
- Ages
- 15 to 99 years
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Child, Adult, Older adult
Key inclusion criteria (21 listed)
- Participants must have diffuse glioma, WHO grades 2-4, histologically confirmed by certified neuropathologistI.
- IDH1 or IDH2 mutation status confirmed by TruSight(TM) Oncology 500 performed in LP, NCI or prior documentation of IDH1 or IDH2 mutation status
- Participants must have received prior treatment (e.g., radiation, conventional chemotherapy, or vorasidenib) prior to disease progression.
- Participants must have recurrent disease, proven histologically or by imaging studies
- Participants who have undergone prior surgical resection are eligible for enrollment to cohorts 1-4.
Key exclusion criteria (16 listed)
- More than one disease relapse in those with initial diagnosis of WHO grade 3-4, or more than two disease relapses in those with initial diagnosis of WHO grade 2 for Phase II. For Phase I enrollment, there are no limits on the number of prior recurrences.
- Prior therapy with:
- Prolonged QTc >470ms as calculated by correction formula on screening electrocardiogram (ECG) (QTCf can be used; QTCb can be used for participants with sinus bradycardia)
- Prior invasive malignancies within the past 3 years prior to study treatment initiation (with the exception of non-melanoma skin cancers, carcinoma in situ of the cervix, melanoma in situ, or any localized cancer for whom the systemic standard of care therapy is not required)
- History of allergic reactions attributed to compounds of similar chemical composition to zotiraciclib, such as flavopiridol
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| ZotiraciclibZotiraciclib will be given orally at the DL1, DL-1, or DL 2 once a day on days 1, 4, 8, 11, 15, 18 of every 28-days cycle (18 cycles total). | Drug | 1 (Closed to Enrollment), 2, 3 |
Primary outcome
To determine 12 months PFS in participants w/ recurrent glioma, IDH1/2-mutant, WHO grade 3 treated w/ zotiraciclib in comparison w/ the established brain tumor database matched for tumor molecular characteristics and clinical prognostic factors
Time frame: 12 Months
Proportion of patients that have progressive disease after 12 months
To estimate recommended phase II dose (RP2D) of zotiraciclib
Time frame: 28 days
Number of DLTs within the DLT Period
3 secondary outcomes
To determine the efficacy of treatment with zotiraciclib in participants with recurrent glioma, IDH1/2-mutant WHO grade 3 in comparison with the established brain tumor database by 3 years PFS rate
Time frame: 3 years
To determine the safety of zotiraciclib in participants with recurrent glioma, IDH1/2-mutant WHO grades 2-4
Time frame: Day 1 of Cycle 0 (Cohort 5) or Day 1 of Cycle 1 (Cohorts 1-4) through 30 days after the study agent was last administered will be collected on the days study drug is administered, and at the safety follow up visit.
To determine the efficacy of treatment with zotiraciclib in participants with recurrent glioma, IDH1/2-mutant WHO grade 3 in comparison with the established brain tumor database by 5 years overall survival (OS) rate
Time frame: 5 years
Results and safety
This study is still under way. Results are not available in the source record yet.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 29 Oct 2026.
- Background: PubMed 27407096Yuan Y, Hess KR, Hilsenbeck SG, Gilbert MR. Bayesian Optimal Interval Design: A Simple and Well-Performing Design for Phase I Oncology Trials. Clin Cancer Res. 2016 Sep 1;22(17):4291-301. doi: 10.1158/1078-0432.CCR-16-0592. Epub 2016 Jul 12.
- Background: PubMed 30668823Miller JJ, Loebel F, Juratli TA, Tummala SS, Williams EA, Batchelor TT, Arrillaga-Romany I, Cahill DP. Accelerated progression of IDH mutant glioma after first recurrence. Neuro Oncol. 2019 May 6;21(5):669-677. doi: 10.1093/neuonc/noz016.
- Background: PubMed 33785481Wu J, Yuan Y, Long Priel DA, Fink D, Peer CJ, Sissung TM, Su YT, Pang Y, Yu G, Butler MK, Mendoza TR, Vera E, Ahmad S, Bryla C, Lindsley M, Grajkowska E, Mentges K, Boris L, Antony R, Garren N, Siegel C, Lollo N, Cordova C, Aboud O, Theeler BJ, Burton EM, Penas-Prado M, Leeper H, Gonzales J, Armstrong TS, Calvo KR, Figg WD, Kuhns DB, Gallin JI, Gilbert MR. Phase I Study of Zotiraciclib in Combination with Temozolomide for Patients with Recurrent High-grade Astrocytomas. Clin Cancer Res. 2021 Jun 15;27(12):3298-3306. doi: 10.1158/1078-0432.CCR-20-4730. Epub 2021 Mar 30.
- Derived from this study: PubMed 40241769Pang Y, Li Q, Sergi Z, Yu G, Kim O, Lu P, Chan M, Sang X, Wang H, Ranjan A, Robey RW, Soheilian F, Tran B, Nunez FJ, Zhang M, Song H, Zhang W, Davis D, Gilbert MR, Gottesman MM, Liu Z, Thomas CJ, Castro MG, Gujral TS, Wu J. Exploiting the therapeutic vulnerability of IDH-mutant gliomas with zotiraciclib. iScience. 2025 Mar 25;28(4):112283. doi: 10.1016/j.isci.2025.112283. eCollection 2025 Apr 18.
- Derived from this study: PubMed 37786680Pang Y, Li Q, Sergi Z, Yu G, Sang X, Kim O, Wang H, Ranjan A, Merchant M, Oudit B, Robey RW, Soheilian F, Tran B, Nunez FJ, Zhang M, Song H, Zhang W, Davis D, Gilbert MR, Gottesman MM, Liu Z, Khan J, Thomas CJ, Castro MG, Gujral TS, Wu J. Exploiting the therapeutic vulnerability of IDH-mutant gliomas with zotiraciclib. bioRxiv [Preprint]. 2024 Jan 2:2023.06.29.547143. doi: 10.1101/2023.06.29.547143.
- NIH Clinical Center Detailed Web PageLink provided by the sponsor.
- Individual participant dataSharing planned: Yes. All IPD recorded in the medical record will be shared with intramural investigators upon request. In addition, all large scale genomic sequencing data will be shared with subscribers to dbGaP.
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part.
Kevin A Camphausen, M.D. principal investigator
National Cancer Institute (NCI)
2 sites in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 1/2 study testing Zotiraciclib in people with Brain Tumor and Cancer, run by National Cancer Institute (NCI) at 2 sites in United States.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 21 inclusion and 16 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: looking for participants now, as of the sponsor's last update on 29 Oct 2026. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 2 sites in United States. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this combined phase mean?
Phase 1 studies test a treatment in a small group of people for the first time or in a new way, mainly to check safety and find the right dose.
Phase 2 studies give the treatment to a larger group to see whether it has the intended effect and to keep checking safety.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
This study is still under way. Results are not available in the source record yet.
How can a doctor refer a patient or contact the research team?
Contact NCI NOB Referral Group ((866) 251-9686, ncinobreferrals@mail.nih.gov), or a site near the patient. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
To determine 12 months PFS in participants w/ recurrent glioma, IDH1/2-mutant, WHO grade 3 treated w/ zotiraciclib in comparison w/ the established brain tumor database matched for tumor molecular characteristics and clinical prognostic factors (time frame: 12 Months). The study lists 2 primary outcomes in all. It is what the study was designed to measure, not a finding.
Where can I read the original study information?
On the ClinicalTrials.gov record for NCT05588141, which also lists 5 linked publications.
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 29 Oct 2026.